Maleic Acid → 5-(4-Chlorobenzyl)-2-{4-[2-(2,2,2-trifluoroethyl)guanidinothiazol-4-yl]butylamino}pyrimid-4-one

HRID 34763Notes

Reaction equation

HRID 34763 reaction equation
[F:1][C:2]([F:19])([F:18])[CH2:3][N:4]=[C:5]([NH2:17])[NH:6][C:7]1[S:8][CH:9]=[C:10]([CH2:12][CH2:13][CH2:14][CH2:15][NH2:16])[N:11]=1.[Cl:20][C:21]1[CH:36]=[CH:35][C:24]([CH2:25][C:26]2[C:27](=[O:34])[NH:28][C:29](SC)=[N:30][CH:31]=2)=[CH:23][CH:22]=1.C(Cl)(Cl)Cl.CO.N.C(O)(=O)/C=C\C(O)=O>CC(C)=O>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([CH2:25][C:26]2[C:27](=[O:34])[NH:28][C:29]([NH:16][CH2:15][CH2:14][CH2:13][CH2:12][C:10]3[N:11]=[C:7]([NH:6][C:5]([NH2:17])=[N:4][CH2:3][C:2]([F:1])([F:18])[F:19])[S:8][CH:9]=3)=[N:30][CH:31]=2)=[CH:35][CH:36]=1

Participants

6

Reactant 4

HCID 444266Maleic AcidHCID 129459805-(4-Chlorobenzyl)-2-methylthiopyrimid-4-oneHCID 212987102-[2-(2,2,2-Trifluoroethyl)-guanidino]-4-(4-aminobutyl)thiazoleHCID 21866414Chloroform methanol ammonia

Product 1

HCID 212987265-(4-Chlorobenzyl)-2-{4-[2-(2,2,2-trifluoroethyl)guanidinothiazol-4-yl]butylamino}pyrimid-4-one

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

An intimate mixture of 2-[2-(2,2,2-trifluoroethyl)guanidino]-4-(4-aminobutyl)thiazole (0.39 g.) and 5-(4-chlorobenzyl)-2-methylthiopyrimid-4-one (0.39 g.) was heated at 150°-160° for 20 min. during which time effervescence occurred. The residue obtained on cooling was subjected to preparative thin layer chromatography using chloroform/methanol/ammonia 90:10:0.5 v/v/v for development. The appropriate zone of the chromatogram was isolated and extracted with hot ethanol/chloroform (50:50 v/v; 200 ml.). Evaporation of the eluate gave a glass which was dissolved in acetone (0.3 ml.) and treated with an excess of a saturated solution of maleic acid in acetone to give a maleate salt of 5-(4-chlorobenzyl)-2-{4-[2-(2,2,2-trifluoroethyl)guanidinothiazol-4-yl]butylamino}pyrimid-4-one as a white powder (0.1 g.) which contained 1.5 moles of maleic acid and 1.5 moles of water of crystallisation. The n.m.r. spectrum in d6 dimethylsulphoxide using tetramethylsilane (δ=0) as internal standard included the following resonances (δ): 3.45 (2H, singlet); 4.1 (2H, multiplet); 7.1 (3H, singlet--maleic acid); 7.45 (1H, singlet) and 8.2 (4H, singlet).

Workup

  1. temperaturewas heated at 150°-160° for 20 min. during which time effervescence
  2. customThe residue obtained
  3. temperatureon cooling
  4. customThe appropriate zone of the chromatogram was isolated
  5. extractionextracted with hot ethanol/chloroform (50:50 v/v; 200 ml.)
  6. customEvaporation of the eluate
  7. customgave a glass which

Sources & evidence

ORD record
ord-a06a2236df2d4abf9e63afe74451eaa7
Source dataset
uspto-grants-1988_08
Patent number
US04762932

Reaction notes

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